Semin Liver Dis 2005; 25(3): 239-250
DOI: 10.1055/s-2005-916330
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Etiopathogenesis of Autoimmunity

Ian R. Mackay1
  • 1Honorary Professor, Department of Biochemistry & Molecular Biology and the Department of Immunology, Monash University, Clayton, Australia
Further Information

Publication History

Publication Date:
06 September 2005 (online)

ABSTRACT

Acquisition by mammals of an adaptive immune system was an evolutionary leap, but occurred at the cost of autoimmunity. The necessity for self-recognition was appreciated in 1900, but autoimmune disease did not become a clinical reality until the 1950s-still the perimeters are indistinct. Autoimmune responses recapitulate the complex events of normal immune responses but cannot shut down. Immune tolerance is established during repertoire development centrally in thymus or bone marrow by deletion of self-reactive immunocytes, and is supplemented peripherally by regulatory T cells (Tregs). A startling discovery is the autoimmune regulator AIRE gene that enables expression of organ-specific autoantigens for intrathymic deletional tolerance of T cells. The origins, activities, and markers of Tregs are under intensive investigation. Of genes implicated in autoimmune, only few are characterized; contributions of environment are similarly uncertain. Time-latency considerations implicate stochastic factors or chance in the etiopathogenesis of autoimmunity, whether they are somatic mutations or successive random gene-environment interactions. Solutions to etiopathogenesis require novel experimental models and finely designed gene-environment studies on human populations. Perhaps immunomodulatory therapies will effect cures before causes are fully understood.

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Ian R Mackay

Department of Biochemistry & Molecular, Monash University Building 13D

Clayton, Victoria 3800, Australia

Email: ian.mackay@med.monash.edu.au